The agent for inducing differentiation of human cancer cell line has a handicap to be used as anti-cancer agent due to its high toxicity. Therefore, the present invention developed an indirubin derivative to be administered in combination with conventional differentiation inducing agent to show the synergic effect for apoptosis of human cancer cell line in a small amount.
Indirubin, one of active ingredients of Chinese herb drug, has been known as anti-cancer property against human cancer cell line. Hoessel et al. disclosed that indirubin is one of CDK (Cyclin-dependent kinase) inhibitor [Nature Cell Biology Vol. 1 May (1999)].
In Korean laying open patent publication No. 2000-6570 ‘Extract of physiological product’, the process for extracting indirubin from indigo plant has been disclosed. Further, in Korean laying open patent publication No. 1998-25557 ‘Process for preparing indirubin using high concentration cell culture’, the process for preparing indirubin in bio-reactor has been disclosed.
Also, the inventors also disclosed a biological process for preparing indirubin using recombinant E. coli harboring novel oxygenase gene in Korean laying open patent publication No. 2003-36580.
In this invention, numerous indirubin derivatives have been synthesized for detecting anti-cancer property of each derivative for selecting the efficacious compound. Through this experiment, novel indirubin derivative has found having excellent anti-cancer property in very low concentration level.